6-42960723-C-T

Position:

• chr6-42960723-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NR_134890.2(CNPY3-GNMT):​n.340-2039C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 1,461,390 control chromosomes in the GnomAD database, including 161,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (16635 hom., cov: 34)
  • Exomes 𝑓: 0.47 (144565 hom.)
• Consequence: CNPY3-GNMT NR_134890.2 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.329

Genes affected

CNPY3-GNMT (HGNC:):

GNMT (HGNC:4415): (glycine N-methyltransferase) The protein encoded by this gene is an enzyme that catalyzes the conversion of S-adenosyl-L-methionine (along with glycine) to S-adenosyl-L-homocysteine and sarcosine. This protein is found in the cytoplasm and acts as a homotetramer. Defects in this gene are a cause of GNMT deficiency (hypermethioninemia). Alternative splicing results in multiple transcript variants. Naturally occurring readthrough transcription occurs between the upstream CNPY3 (canopy FGF signaling regulator 3) gene and this gene and is represented with GeneID:107080644. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 6-42960723-C-T is Benign according to our data. Variant chr6-42960723-C-T is described in ClinVar as [Benign]. Clinvar id is 1283888.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNPY3-GNMT	NR_134890.2	n.340-2039C>T		intron_variant, non_coding_transcript_variant
GNMT	NM_018960.6			upstream_gene_variant		ENST00000372808.4	NP_061833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNMT	ENST00000372808.4			upstream_gene_variant		1	NM_018960.6	ENSP00000361894	P1

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69996 AN: 152082 Hom.: 16624 Cov.: 34

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.459

GnomAD3 exomes AF: 0.391 AC: 34529 AN: 88392 Hom.: 7518 AF XY: 0.402 AC XY: 18517 AN XY: 46108

Gnomad AFR exome AF: 0.521

Gnomad AMR exome AF: 0.279

Gnomad ASJ exome AF: 0.431

Gnomad EAS exome AF: 0.126

Gnomad SAS exome AF: 0.448

Gnomad FIN exome AF: 0.421

Gnomad NFE exome AF: 0.476

Gnomad OTH exome AF: 0.430

GnomAD4 exome AF: 0.465 AC: 608822 AN: 1309190 Hom.: 144565 Cov.: 27 AF XY: 0.466 AC XY: 296459 AN XY: 636678

Gnomad4 AFR exome AF: 0.518

Gnomad4 AMR exome AF: 0.299

Gnomad4 ASJ exome AF: 0.421

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.461

Gnomad4 FIN exome AF: 0.413

Gnomad4 NFE exome AF: 0.483

Gnomad4 OTH exome AF: 0.449

GnomAD4 genome AF: 0.460 AC: 70048 AN: 152200 Hom.: 16635 Cov.: 34 AF XY: 0.455 AC XY: 33823 AN XY: 74398

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.457

Alfa AF: 0.459 Hom.: 6751

Bravo AF: 0.455

Asia WGS AF: 0.290 AC: 1009 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.8
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10948059; hg19: chr6-42928461; COSMIC: COSV55102851;